Medication against breast cancer and related diseases

Abstract

The present invention relates to novel uses of a steroid compound, which specifically binds to the androgen receptor (AR) but which is not metabolized by aromatase to a process for their preparation, to pharmaceutical compositions containing them, and to the use of said compounds for the prophylaxis and / or treatment of hormone-dependent or hormone receptor regulated cancers in mammals.

Description

[0001]This is a National Phase Application in the United States of International Patent Application No. PCT / EP2007 / 004221 filed May 11, 2007, which claims priority on European Patent Application No. 06 009 894.4, filed May 12, 2006 and U.S. Provisional Application No. 60 / 747,124, filed May 12, 2006. The entire disclosures of the above patent applications are hereby incorporated by reference.BACKGROUND OF THE INVENTION[0002]1. Field of the Invention[0003]The present invention relates to novel uses of 4,17β-dihydroxyandrost-4-ene-3-one (hereinafter 4-hydroxytestosterone) and its salts and esters, to a process for their preparation, to pharmaceutical compositions containing them, and to the use of said compounds for the prophylaxis and treatment of certain diseases in mammals, in particular cancers.[0004]2. Discussion of the Related Art[0005]After colorectal cancer breast cancer is the most frequent cancer disease in the western world despite the fact that it affects almost exclusively...

AI Technical Summary

Benefits of technology

The invention is a medicament that can be used for breast cancer prevention and treatment. It has the advantage of being able to prevent recurrences of breast cancer and the development of a new cancer in the opposite breast after treatment. The medicament can also be used for high-risk women who have a genetic predisposition for breast cancer. The treatment is safe and effective with minimal systemic side effects, and can be started before symptoms are noticed. The medicament can be applied over a long period of time and is easy to penetrate fatty tissue.

Problems solved by technology

A particular complication of breast carcinomas is the high potential of metastatic spread into other organs particularly liver, brain, bones and the skin.

Clinical studies conducted with estrogen-receptor (ER) antagonists and aromatase inhibitors however showed that these compounds were not able to exert a significant and sufficient inhibitory effect on tumour proliferation and / or growth.

For example, TAMOXIFEN® based therapy suffers from drawbacks such as tachyphylaxy (therapy failure) and the fact that its effects in some cells are estrogen-like (e.g. risk for thrombosis and edometrial cancer) being the reason that TAMOXIFEN® can not be administered for a period longer than 3 to 5 years.

Newer drugs such as aromatase inhibitors can in principle only be used in post-menopausal women and, furthermore, are only effective on ER-positive tumours.

“Hormonal” treatment with selective estrogen receptor modulators (SERMs) such as tamoxifen or raloxifen or aromatase-inhibitors has proven to be ineffective.

There is no “hormonal” treatment for ER-negative breast cancers so far.

It clinical usefulness however is hampered by the fact that it undergoes rapid metabolization to either estradiol or dihydrotestosterone (DHT).

However, in terms of therapeutic concepts, WO 2005 / 062760 is limited to control AR itself, not androgen mediated activity, in the context of mammary gland development by inhibiting AR activity.

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